(1)背景:SLC22家族的许多转运蛋白(例如,OAT1,OAT3,OCT2,URAT1和OCTN2)在肾脏中高表达。他们运输毒品,代谢物,信号分子,抗氧化剂,营养素,和肠道微生物组产品。根据遥感和信号理论,SLC22转运蛋白在细胞器之间的小分子通讯中起关键作用,细胞和器官以及身体和肠道微生物组之间。这提出了关于SLC22转运蛋白在癌症生物学和治疗中的潜在作用的问题。(2)结果:在TCGA中发现的两个肾细胞癌RNA-seq数据集中,KIRC和KIRP,与正常肾脏相比,有多个差异表达(DE)SLC22转运蛋白基因。其中包括SLC22A6、SLC22A7、SLC22A8、SLC22A12和SLC22A13。患有疾病的患者在总体生存率和大多数这些DE基因的表达之间存在关联。在KIRC,通过病理肿瘤特征对患者数据进行分层,揭示了SLC22A2,SLC22A6和SLC22A12在疾病进展中的重要性.将SLC22与ADME基因结合的相互作用网络支持SLC22转运蛋白和其他转运蛋白(ABCG2,SLC47A1)在疾病进展中的中心地位。(3)含义:许多这些基因是尿酸转运蛋白的事实很有趣,因为尿酸水平的改变与肾癌有关。此外,这些基因在加工代谢物和化疗化合物中发挥关键作用,从而使它们成为潜在的治疗靶点。最后,我们的分析提出了这样一种可能性,即目前的方法可能对某些SLC22低表达且仅局部疾病的肾癌患者治疗不足,而对SLC22高表达的患者可能过度治疗更晚期的疾病.需要临床研究来研究这些可能性。
(1) Background: Many transporters of the
SLC22 family (e.g., OAT1, OAT3, OCT2, URAT1, and OCTN2) are highly expressed in the kidney. They transport drugs, metabolites, signaling molecules, antioxidants, nutrients, and gut microbiome products. According to the Remote Sensing and Signaling Theory,
SLC22 transporters play a critical role in small molecule communication between organelles, cells and organs as well as between the body and the gut microbiome. This raises the question about the potential role of
SLC22 transporters in cancer biology and treatment. (2) Results: In two renal cell carcinoma RNA-seq datasets found in TCGA, KIRC and KIRP, there were multiple differentially expressed (DE) SLC22 transporter genes compared to normal kidney. These included SLC22A6, SLC22A7, SLC22A8, SLC22A12, and SLC22A13. The patients with disease had an association between overall survival and expression for most of these DE genes. In KIRC, the stratification of patient data by pathological tumor characteristics revealed the importance of SLC22A2, SLC22A6, and SLC22A12 in disease progression. Interaction networks combining the
SLC22 with ADME genes supported the centrality of
SLC22 transporters and other transporters (ABCG2, SLC47A1) in disease progression. (3) Implications: The fact that many of these genes are uric acid transporters is interesting because altered uric acid levels have been associated with kidney cancer. Moreover, these genes play key roles in processing metabolites and chemotherapeutic compounds, thus making them potential therapeutic targets. Finally, our analyses raise the possibility that current approaches may undertreat certain kidney cancer patients with low
SLC22 expression and only localized disease while possibly overtreating more advanced disease in patients with higher SLC22 expression. Clinical studies are needed to investigate these possibilities.